Thoracic surgery: risk factors for postoperative complications of lung resection

Cirurgia torácica: fatores de risco para complicações pós-operatórias na ressecção pulmonar

ARTIGO ORIGINAL

Thoracic surgery: risk factors for postoperative complications of lung resection

Cirurgia torácica: fatores de risco para complicações pós-operatórias na ressecção pulmonar

Eduardo Oliveira Fernandes^I; Cassiano Teixeira^II; Luis Carlos Correa da Silva^III

^IMD, Coordinator of the General Medicine Residency Program at Grupo Hospitalar Nossa Senhora da Conceição, Porto Alegre, RS

^IIMD, Intensive Care Medicine at Complexo Hospitalar da Santa Casa de Porto Alegre; Professor at Clínica Médica, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS

^IIIMD, Pneumologist at Pavilhão Pereira Filho da Santa Casa de Porto Alegre; Coordinator of the Pulmonary Function Test Laboratory at Pavilhão Pereira Filho and Professor of the Pneumology Department at UFCSPA, Porto Alegre, RS

^{Correspondence to}

SUMMARY

OBJECTIVE: To identify preoperative and transoperative risks factors for postoperative complications developed in lung resection surgery.

METHODS: During 14 months; 189 patients underwent pulmonary resection and were enrolled to the study. After a clinical interview, patients were evaluated by laboratory, pulmonary function tests and radiography, submitted to a surgical procedure, and were followed during their stay in the ICU and hospital, evaluating postoperatory complications and death.

RESULTS: The postoperative rate of complications was 52.9%: respiratory (34.3%), infectious (31%), and cardiovascular (21.4%). Respiratory complications were related to smoking (p < 0.01, RR 2.31), airway obstruction by spirometry (p = 0.01, RR 2.60), presence of anemia (p < 0.01, RR 2.13), and prolonged protrombine time [PT] (p = 0.03, RR 1.77). Infection complications were related to smoking (p < 0.01, RR 2.69), airway obstruction by spirometry (p = 0.01, RR 3.31), presence of anemia (p < 0.01, RR 2.10), and prolonged PT (p = 0.03, RR 2.29). Cardiovascular problems were related with older age (p < 0.01, RR 2.66), cigarette smoking (p < 0.01, RR 4.55), and hypoxemia (p = 0.03, RR 2.43). The postoperative mortality rate was 7.1%.

CONCLUSION: A preoperative evaluation can provide a suitable and safe postoperative prediction of complications in patients submitted to lung resection. Patients with COPD, hypoxemic, older, and anemic patients must be classified as high-risk for developing these complications.

Keywords: Thoracic surgery; preoperative care; risk factors; prognosis hospital mortality.

RESUMO

OBJETIVO: Identificar os fatores de risco pré e transoperatórios para o desenvolvimento de complicações pós-operatórias na cirurgia de ressecção pulmonar.

INTRODUÇÃO: Os pacientes submetidos à cirurgia de ressecção pulmonar desenvolvem graves e frequentes complicações pós-operatórias. A identificação dos fatores de risco para o desenvolvimento das mesmas é fundamental na predição das complicações no pós-operatório.

MÉTODOS: Durante 14 meses, 189 pacientes foram submetidos à intervenção cirúrgica torácica e foram incluídos no estudo. Depois de uma entrevista clínica, os pacientes foram avaliados por exames laboratoriais, espirometria e exames de imagem. Os mesmos foram submetidos ao procedimento cirúrgico e foram seguidos durante a sua permanência na UTI e no hospital, avaliando as complicações pós-operatórias e o risco de morte.

RESULTADOS: A taxa de complicações pós-operatórias foi de 52,9%, principalmente respiratórias (34,3%), infecciosas (31%) e cardiovasculares (21,4%). As complicações respiratórias foram relacionadas ao tabagismo (p < 0,01, RR 2,31), obstrução das vias aéreas (p = 0,01, RR 2,60), presença de anemia (p < 0,01, RR 2.13), e prolongado tempo de protrombina [PT] (p = 0,03, RR 1,77). As complicações infecciosas estiveram relacionados ao tabagismo (p < 0,01, RR 2,69), obstrução de vias aéreas (p = 0,01, RR 3,31), presença de anemia (p < 0,01, RR 2.10) e TP prolongado (p = 0,03, RR 2,29 ). Os problemas cardiovasculares, especialmente a presença de arritmias, foram relacionados com idade mais avançada (p < 0,01, RR 2,66), tabagismo (p < 0,01, RR 4,55) e hipoxemia (p = 0,03, RR 2,43). A taxa de mortalidade pós-operatória foi de 7,1%.

CONCLUSÃO: A identificação dos fatores de risco pode predizer complicações pós-operatórias nos pacientes submetidos a ressecção pulmonar. Pacientes com DPOC, hipoxêmicos, idosos e anêmicos devem ser classificados como de alto risco para o desenvolvimento de complicações.

Unitermos: Cirurgia torácica; cuidados pré-operatórios; fatores de risco; prognóstico; mortalidade hospitalar.

Introduction

Benefits of pulmonary surgical treatment are well-established. Life expectation of patients with non-small cell lung cancer is increased to 48 months, compared to 17 months of survival of patients submitted only to medical treatment¹. Furthermore, surgery for bronchiectasis increases the quality of life² and survival of these patients³. However, postoperative complications are a significant cause of morbidity and mortality in patients submitted to thoracic or abdominal surgeries⁴.

Managing of these patients requires an understanding of the predictable changes in pulmonary physiology occurring with surgery and anesthesia as well as a knowledge of factors associated with development of postsurgical complications. The surgical procedure causes reduction of lung capacity (represented by forced vital capacity [FVC] and forced expiratory volume in one second [FEV₁]) diaphragm dysfunction, impairs gas exchange, and cough and mucociliary clearance leading to development of microatelectasis and postoperative hypoxemia^4,5. These modifications are exacerbated in chronic obstructive pulmonary disease [COPD]^6,7, as well as in older patients⁸, survivors of recent myocardial infarction⁹, in starvation¹⁰ and smoking patients¹¹.

The patients submitted to pulmonary resection procedures developed severe and frequent postoperative complications, so these patients frequently are submitted to the preoperative risk evaluation¹². Advances in surgical and anesthetic techniques, combined with a detailed preoperative and sophisticated perioperative assessment, have contributed to an increasing number of adults undergoing these procedures^12-14.

The objective of this study was to identify preoperative, and transoperative risks factors for developed postoperative complications in lung resection surgery.

Methods

Patient management

All patients submitted to lung surgery at a reference for clinical and surgical lung diseases hospital over a 14 month period were prospectively studied. All subjects enrolled underwent elective lung resection surgeries (lobectomy and pneumonectomy) with or without chest wall resection due to cancer, abscesses, or bronchiectasies. Exclusion criteria were: < 18 years of age, palliative resection, lung transplantation, thoracic trauma, thoracic surgery with no lung resection, thoracoscopy or thoracotomy for lung nodule biopsy, tracheostomy, emergency surgery, and informed consent declined. The study was approved by the Ethics in Research Committee of both hospitals and Informed Consent was obtained from all patients or next of kin.

The preoperative evaluation included a complete history, physical examination, blood cell count, biochemical profile, chest film, 12-lead ECG, and pulmonary function tests. When FEV₁ was < 60% of the predicted value, a differential lung perfusion scan was performed. Patients with borderline spirometric results or impaired exercise tolerance underwent a cardiopulmonary exercise test on a bicycle ergometer. Transthoracic echocardiography, thallium-dipyridamole myocardial scintigraphy, or coronary angiogram were performed in patients with risk factors for coronary artery disease [CAD] and in those patients with low functional capacity, according to guidelines published by the American College of Physicians [ACP]^15,16. Preoperatively, as routine a thoracic epidural catheter was inserted, except for patients who refused placement of the catheter, patients with coagulation disorders, acute neurologic problems, local or systemic infections, or technical failures (i.e., catheter malpositioning or malfunction). Prophylactic antibiotic therapy (i.e., cefuroxime, 1.5 g every 8 h for 24 h) was administered routinely. All patients were operated by one of three specialized surgeons in thoracic surgeries and were managed by the same team of anesthesiologists and chest critical care physicians.

After surgery, patients were monitored for at least 48 h in the postanesthesia care unit or intensive care unit [ICU] to provide intensive nursing and respiratory care with emphasis on pain control, diaphragmatic breathing, aggressive pulmonary toilet by aggressive postoperative physical therapy, as well as early mobilization, ambulation, and feeding. Intravenous [IV] fluid infusion was limited to compensate for volume of blood loss with 0.9% saline solution and to replace evaporation loss with 5% glucose in saline solution at a rate of 1 mL/kg/h. Postoperative pain was assessed at rest and during coughing with a visual analog scale. The analgesic regimen was titrated to keep the visual analog scale at < 4/10 using either IV (morphine sulfate and nonsteroidal anti-inflammatory drugs) or epidural catheter (morphine sulfate) from 2 to 4 days.

Data collection and extraction

The preoperative data registered during standard interview and physical exam included: age, gender, smoking history (positive when smoking more than 20 pack years), presence of concomitant diseases (diabetes, cardiovascular, renal, and pulmonary disease). Other preoperative data registered were: arterial blood gases on air, blood cell count, biochemical profile, pulmonary function test [PFT](FEV1 and FVC as percentage of predicted), 12-lead ECG, type of malignancy, and informed consent. Diagnosis of chronic obstrutive pulmonary disease [COPD] was based on a history of myocardial infarction or angina, or typical Q waves seen on the ECG. Elevated blood pressure, arrhythmias, and diabetes mellitus requiring medication were considered significant comorbidities. Peripheral artery disease was defined by clinical evidence (i.e., claudication at exercise and past or current vascular surgery) or arteriography. Diagnosis of COPD was based on criteria of the American Thoracic Society [ATS] and on results of pulmonary functional tests (i.e., FEV1/FVC, < 70% of predicted value)17. Specific cutoff points were selected to define risk factors: (a) advanced age: > 65 years; (b) moderate to severe COPD: FVC or FEV1 < 60% of the predicted; (c) hypoxemia in room air: PaO2 < 60 mmHg; (d) hypercapnia: PaCO2 > 45 mmHg; (e) lymphocytopenia: lymphocyte count < 1500/µL; (f) increased hemorrhage risk: prothrombin time [PT] > 13 sec; and (g) anemia: hemoglobin < 10 g/dL.

Intraoperative risk factors studied were perioperative estimated blood loss (3 or more packed red blood cells requirement), and occurrence of a hemodynamic instability defined as need for IV vasopressor or IV vasodilator during procedure. Experience of the surgeon and anesthetist were not recorded since all surgical procedures were performed by the same surgical and anesthesia team with more than 20 years of experience in management of lung diseases. The duration of the surgical procedure (from skin incision to closure) was not registered.

Patients were followed during ICU and hospital stay to evaluate postoperative complications and mortality. Complications were grouped as (a) respiratory: atelectasis, endotracheal reintubation, mechanical ventilation requirement > 24 h, and pleural air leak for more than 7 days; (b) cardiovascular: arrhythmias, hemodynamic instability with need for inotropic or vasodilators and coronary acute syndrome; (c) infectious: pneumonia (defined as new and persistent lung infiltrates at chest film, axillary temperature > 38.5ºC, and macroscopically proven purulent tracheal secretions), wound infection and pleural empyema; (d) metabolic: hyperglycemia (need of continuous insulin), eletrolite disturbances, and acute renal insufficiency (need of dyalisis); and (e) prognosis (survival or death). Severe postoperative complications were considered: endotracheal reintubation, hemodynamic instability with need for inotropic or vasodilators, coronary acute syndrome, pneumonia, pleural empyema, acute renal insufficiency, and death. Each patient could have one or more complications therefore, the number of complications was greater than the number of patients. Operative mortality was defined as death until 30^th day after procedure.

Data were classified as preoperative, and intraoperative, risk factors and as postoperative complications.

Statistical analysis

Data were analyzed using statistical software (Epi-Info version 6.0). Univariate analysis was carried out using the χ² test or Fisher's Exact Test for categorical variables and the Wilcoxon or Kruskal-Wallis test for continuous variables. Multivariate analysis (multiple logistic regression) was used to determine the relative risk (RR) and odds ratio (OR) and their 95% confidence intervals (95%CI) in variables with a p value <0.05 in univariate analysis for postoperative complications and death. All tests were two sided, and p values of < 0.05 were considered statistically significant.

Results

Study population

During the 14 months reference period, 532 thoracic surgeries were performed, and 189 patients were prospectively enrolled, and submitted to elective lung resection surgery (lung lobectomy and pneumonectomy). Sixty-nine point three percent were male, mean age of 62.2 ± 12.4 years, and 104 smokers (mean cigarette consumption was 49 pack years). More men than women were smoking (92.1% and 53%, respectively). Lung cancer was present in 75.5% of the cases. Preoperative clinical characteristics of patients, laboratory data and type of surgery as well as intraoperatory data are presented in Table 1.

Postoperative complications

Postoperative complications are presented in Table 1. The postoperative rate of complications was 52.9%: respiratory (34.3%), infectious (31%), cardiovascular (21.4%), and metabolic (1.4%). The mortality rate was 13.7%, and mostly due to sepsis (52.9%) follow pneumonia (29.7%) or pleural empyema (8.6%).

Respiratory postoperative complications were related with smoking (p < 0.01, RR 2.31 [95% CI 1.92 - 2.95]), airway obstruction in spirometry (p = 0.01, RR 2.6 [95% CI 1.8 - 3.1]), presence of anemia (p < 0.01, RR 2.13 [95% CI 1.12 - 3.92]), and prolonged PT (p = 0.03, RR 1.77 [95% CI 0.94 - 4.16]). Delay in extubation was the only respiratory complication that correlated individually with the cigarette smoking risk factor (p = 0.02, RR 2.76 [95%CI 1.53 - 3.38]). Table 2 shows the relationship between postoperative complications and preoperative characteristics, type of surgery, and intraoperative data.

Infectious postoperative complications were related with smoking (p < 0.01, RR 2.69 [95% CI 1.28 - 3.54]), airway obstruction in spirometry (p = 0.01, RR 3.31 [95% CI 2.56 - 3.85]), presence of anemia (p < 0.01, RR 2.10 [95% CI 1.25 - 3.12]), and prolonged PT (p = 0.03, RR 2.29 [95% CI 1.82 - 3.17). Pneumonia was the only infectious complication correlated with smoking (p < 0.01, RR 2.69 [95% CI 2.42 - 2.98]), airway obstruction in spirometry (p < 0.01, RR 3.31 [95% CI 2.96 - 3.77]), presence of anemia (p < 0.01, RR 2.12 [95% CI 1.37 - 3.75]), and prolonged PT (p < 0.01, RR 2.26 [95% CI 0.76 - 5.78]). Pre and intraoperative risk factors were unable to predict occurrence of wound infection or pleural empyema.

Cardiovascular problems were related with older age (p < 0.01, RR 2.66 [95% CI 2.21 - 2.96]), cigarette smoking (p < 0.01, RR 4.55 [95% CI 3.65 - 5.95]), and hypoxemia (p = 0.03, RR 2.43 [95% CI 1.02 - 3.68]).

Metabolic postoperative problems were not predicted by the presence of pre or intraoperative risks. Pneumonectomies did not present more postsurgical complications when compared with lobectomies. When evaluating arterial blood gases, hypercapnia did not relate with complications. Detailed analysis of preoperative ECG did not predict risk of surgical complications. It is important to remember that patients could have one or more postsurgical complications.

Postoperative mortality

Smoking (p = 0.01, RR 3.76 [95% CI 2.54 - 5.02]) and hypoxemia (p = 0.02, RR 3.56 [95% CI 3.08 - 3.97]) were the preoperative risk factors that increased patient postoperative mortality. Although requirement for intraoperative blood transfusion did no increase postoperative complications individually, it increased postoperative mortality (p = 0.01, RR 4.53 [95% CI 1.72 - 7.65]), as well as the need of pneumonectomy (p < 0.01, RR 2.31 [95% CI 1.22 - 4.19]).

Table 3 shows the increase of mortality due to finding of postsurgical complications.

Discussion

Thoracic surgeries are procedures associated with relatively high rates of postsurgical complications¹⁸. Incidence of pulmonary complications is uncertain, due to the variability of definitions used by different authors¹⁹. Although physicians involved in preoperative evaluations can base surgical risk assessment on extensive research, their ability to do so correctly is limited by methodological problems in literature such as poor standardization and definition of postoperative complications, inadequate blinding of observers, selection bias, limitation by study size, and reporting of non-clinical significant complications (e.g., microatelectasis) ²⁰.

Patient-related risk factors

Age. Some authors consider advanced age as a risk factor for mortality and perioperative complications^8,21-24, others disagree with it^25-30. Ergina et al.³¹ demonstrated that older patients have more respiratory or cardiovascular complications, and Tisi et al.⁷ suggested that it was due to the physiological effect of aging (reduction of the vital capacity, peakflow, elastic lung retraction, and increase of residual lung volume). Despite early suggestions of an increased risk of pulmonary complications with advanced age, this is not an independent risk factor for pulmonary complications. The healthy status of a patient, mainly cardiorespiratory seems to be much more important than age²⁶. In our study, those older 65 years had no increase of postoperative mortality, and in agreement with Kroenke et al.²³, we observed an association with cardiovascular complications.

Smoking. The beneficial effects of smoking cessation, including improvement in ciliary and small airway function and a decrease in sputum production, occur gradually over several weeks. The risk is highest in patients who were smoking within the last 2 months, and patients who had quit smoking for more than 6 months, have a risk similar to those who do not smoke. Postoperative morbidity did not decrease in patients who had quit smoking for less than 4 weeks³². Our study showed increase of pulmonary and cardiovascular complications as well as increase of mortality rates.

Pulmonary function tests. Results of several retrospective studies of routine preoperative PFT disclosed only a marginal benefit in predicting postoperative complications in patients except in those undergoing lung resection. PFT could be used to identify high-risk patients for whom aggressive perioperative management is warranted. The ACP consensus statement^15,16,33 suggests the following indications for preoperative PFT: (a) patients undergoing cardiac or upper abdominal surgery with a history of smoking or dyspnea; (b) patients undergoing lower abdominal surgery if dyspnea or history of smoking indicates prolonged surgery; (c) patients undergoing orthopedic surgery with uncharacterized lung disease; (d) patients undergoing lung resection; (e) older than 60 years of age; (f) positive smoking history; (g) presence of pulmonary disease; and (h) presence of pulmonary symptoms. PFT results should not be the sole reason to change plans necessary for surgery.

PFT remain the standard screening tests performed before pulmonary resection. It is generally agreed that a minimum value of FEV₁ is required preoperatively (2 L before pneumonectomy and 1.5 L lobectomy, respectively) and that further cardiopulmonary testing is needed in patients with marginal lung function³⁴. Variable cut-off values of FEV₁ (ranging from 35% to 80%) have been arbitrarily chosen to assess the severity of COPD and to predict the risk for pulmonary complications, but preoperative FEV₁ less than 60% is still a main predictor of perioperative mortality and respiratory morbidity³⁵.

COPD. Patients with severe COPD are 6 times more likely to have a major postoperative complication³⁵. Elective surgery should be deferred in patients who are symptomatic, have poor exercise capacity, or have acute exacerbation. PFT results do not facilitate identification of the high-risk patients or of severity of dysfunction when risk of surgery is forbidding. Therefore, surgery should never be withheld based on PFT results³³. Patients with severe COPD, classified as very high risk, may undergo surgery and will face a moderate risk of postoperative complications (29%)^23,35. We use the Kroenke et al.²³ criteria and more than 40% of the patients presented with severe COPD based upon spirometric findings, and identifing an association between FEV₁ and respiratory, cardiovascular complications.

Arterial blood gases. A PaCO₂ of more than 45 mmHg often occurs in persons with severe COPD and indicates a high risk, although it is not necessarily prohibitive for surgery^7,36,37. Hypoxemia is not a significant predictor of complications³⁶. In our study, we verify that hypoxemia was associated with cardiac complications, principally occurrence of arrhythmias. We did not find an association between hypercapnia and prognosis, perhaps due to the small number of patients with this alteration.

Anemia. Anemia is present in 10% of patients admitted to general hospitals³⁸. Hemoglobin values above of 10 g/dL do not significantly reduce oxygen transport and treatment is not required before surgery, and almost 45% of our patients had anemia, based in this criteria. Our data showed that anemic patients had more respiratory and infectious complications, probably due to nutritional deficiencies not identified during the preoperative evaluation.

Lymphocytopenia. This is a malnutrition marker just as albumin level, and malnutrition is a risk of morbidity and mortality in critical care and surgical patients^39,40. Moreover, patients submitted to thoracic surgery, frequently have cancer and are smokers; predisposing factors to malnutrition. Busch et al.⁴¹, in 106 patients submitted to lung surgery due to bronchogenic cancer, did not correlate lymphocytopenia with higher postoperative complications, in agreement with our study data.

Prothrombin time. High values of PT are a contraindication for surgical procedures, due to an increase of hemorrhagic complications⁴². Our data showed increased respiratory complications, which in our opinion is due to PT being a marker of hepatic synthesis capacity and not because of coagulation defects⁴³.

Intraoperative risk factors

Perioperative blood transfusion. Whitson et al.⁴⁴ showed that perioperative blood transfusion was associated with increased postoperative complications (53.5% vs. 30.5%, p < 0.001). In our study, blood transfusion was associated with an increased operative mortality (3.4% vs. 1.7%, p = 0.005) and length of stay after surgery (median 6 vs. 5 days, p < 0.001).

Postoperative complications

Keagy et al.^45,46 reported on 369 patients, 244 had postoperative complications during follow-up of 30 days, mainly cardiovascular (41%) and pulmonary (21%). Wahi et al.²⁸, in 197 pneumonectomies followed-up during 30 days, showed 23% of arrhythmias and prolonged MV in 9.1% of the cases. Ferguson et al.⁴⁷, evaluating 271 patients, showed postoperative complications in 52% of the cases; and Asamura et al.⁴⁸, in 267 patients submitted to thoracotomy, found 23.6% of arrhythmias. Our study found respiratory complications in 34.3% of the cases, and pneumonia in 29.7% of the cases.

Postoperative mortality

Some authors^34,45-47,49 described variables postoperative mortality rates (2.8% - 12.6%), and the higher mortality rates found in patients submitted to pneumonectomies (7.1% - 27.4%)^28,47,49. Ginsberg et al.⁵⁰, reviewed 2,220 patients submitted to thoracotomies in North-American and Canadian reference hospitals, and showed mortality postsegmentectomies of 1.4%, after lobectomies of 2.9%, and after pneumonectomies of 6.7%. Our data demonstrated global mortality of 7.1%, and pneumonectomy mortality of 19.4%.

Strengths and limitations: We believe that the strengths of this paper are: (a) large sample; (b) research developed in a hospital specialized in respiratory diseases; and (c) follow-up of all patients studied. We are mindful of several limitations related to: (a) design of the study (cohort study); (b) no evaluation of preoperative creatinine values (despite all patients have values lower than 1.5 mg/dL); (c) single center report; (d) no evaluation of intraoperative data (e.g. duration of the surgery or anesthesia, and intraoperative fluid balance); and (e) no evaluation of stairs climbing test in patients with preoperative VEF₁ < 2 L⁵¹.

Conclusion

In an era of progressive cost containment and public scrutiny, the wisdom of aggressive preoperative evaluations for all surgical candidates have been questioned. Current data quantify the risks and morbidities associated with the care of seriously ill patients with coronary artery disease and demonstrate the need for professional and public discussions focusing on the association of a high preoperative risk status and the consumption of resources. A concise and standarized preoperative evaluation can provide a suitable and safe postoperative prediction of complications in patients submitted to lung resection, and patients with COPD, hypoxemic, older, anemic patients, and need of pneumonectomy must be classified as high-risk for develop postoperative complications.

Submitted on: 11/27/2010

Approved on: 03/17/2011

Conflict of interest: None.

Study conducted at Pavilhão Pereira Filho da Santa Casa de Porto Alegre, Porto Alegre, RS

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Publication Dates

• Publication in this collection
  09 June 2011
• Date of issue
  June 2011

History

• Received
  27 Nov 2010
• Accepted
  17 Mar 2011